Heyman B, Pilström L, Shulman M J
Department of Immunology, Uppsala University, Sweden.
J Exp Med. 1988 Jun 1;167(6):1999-2004. doi: 10.1084/jem.167.6.1999.
The ability of IgM antibodies to specifically enhance the thymus-dependent humoral immune response to particulate antigens is well documented. We have used two approaches to test whether complement factors play a role in this process. First, mice were depleted of C3 by treatment with cobra venom factor (CVF) and then immunized with SRBC with or without IgM-anti-SRBC. CVF treatment severely impaired the capacity of IgM to induce an enhanced anti-SRBC response. Moreover, it was shown that IgM can potentiate the response in C5-deficient AKR mice, thus demonstrating that the complement factors acting before C5 are the crucial ones. A second test compared the enhancing properties of two monoclonal IgM-anti-TNP antibodies where, because of a point mutation in the mu chain constant region, one of the antibodies is impaired in its capacity to activate complement. We show that the mutant antibody lacks the enhancing properties of the wild-type IgM. Activation of C3 by IgM antibodies as well as localization of antigen in the spleen seem to be necessary steps in the IgM-mediated enhancement of antibody responses. Our data offer an explanation to the immunosuppression described in CVF-treated animals as well as the low humoral immune responses in certain hereditary complement deficiencies. It is suggested that IgM indeed has an important physiological function in enhancing antibody responses to foreign substances.
IgM抗体特异性增强对颗粒性抗原的胸腺依赖性体液免疫反应的能力已有充分记录。我们采用了两种方法来测试补体因子是否在此过程中发挥作用。首先，用眼镜蛇毒因子（CVF）处理小鼠以耗尽C3，然后用SRBC免疫，同时给予或不给予IgM抗SRBC。CVF处理严重损害了IgM诱导增强的抗SRBC反应的能力。此外，研究表明IgM可以增强C5缺陷型AKR小鼠的反应，从而证明在C5之前起作用的补体因子是关键因素。第二项测试比较了两种单克隆IgM抗TNP抗体的增强特性，由于μ链恒定区的点突变，其中一种抗体激活补体的能力受损。我们发现突变抗体缺乏野生型IgM的增强特性。IgM抗体激活C3以及抗原在脾脏中的定位似乎是IgM介导的抗体反应增强的必要步骤。我们的数据解释了CVF处理动物中描述的免疫抑制以及某些遗传性补体缺陷中的低体液免疫反应。提示IgM在增强对外源物质的抗体反应中确实具有重要的生理功能。
